Redox proteomic analysis reveals an important role for protein oxidative modifications in hypoxia adaptation of Aspergillus fumigatus

ABSTRACT: In the site of infection, the human fungal pathogen Aspergillus fumigatus faces dynamic changes in oxygen concentrations. The ability to survive in severely hypoxic environments during host invasion is one of important virulence traits of A. fumigatus. Therefore, investigation of hypoxia adaptation mechanisms of this pathogen may suggest potential targets for the development of antifungal therapies. Currently, an increasing number of reports has demonstrated that elevated production of intracellular reactive oxygen species (ROS) under low oxygen conditions plays a regulatory role in modulating cellular responses for adaptation to hypoxia. Our results confirmed raised amounts of intracellular ROS in A. fumigatus exposed to decreased oxygen levels. Moreover, nuclear accumulation of the oxidative stress response transcriptional factor AfYap1 was observed after two hours of low oxygen cultivation. For further analysis, we applied iodo-TMT labeling of redox-sensitive cysteine residues to identify proteins, which get reversibly oxidized and therefore regulated by hypoxic ROS after shifting oxygen content in the culture from 21% to 0.2%. For instance, proteins with important roles in maintaining redox balance and protein folding were modified after one hour of hypoxic cultivation. Redox proteomic investigation also revealed that a mitochondrial protein, designated as Coa6, was regulated by hypoxic ROS. A homologous protein in Saccharomyces cerevisiae was shown to be important for a respiratory chain complex IV assembly. Deletion of the gene encoding this protein in A. fumigatus resulted in complete absence of hypoxic growth, suggesting the significance of complex IV during adaptation of A. fumigatus to oxygen limiting conditions.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Neosartorya Fumigata (aspergillus Fumigatus)

SUBMITTER: Thomas Krüger  

LAB HEAD: Olaf Kniemeyer

PROVIDER: PXD006822 | Pride | 2019-01-16

REPOSITORIES: Pride